title: Identification of brain tumour initiating cells using the stem cell marker aldehyde dehydrogenase.
abstract: Aldehyde dehydrogenase (ALDH) has been identified in stem cells from both normal and cancerous tissues. This study aimed to evaluate the potential of ALDH as a universal brain tumour initiating cell (BTIC) marker applicable to primary brain tumours and their biological role in maintaining stem cell status. Cells from various primary brain tumours (24paediatric and 6 adult brain tumours) were stained with Aldefluor and sorted by flow cytometry. We investigated the impact of ALDH expression on BTIC characteristics in vitro and on tumourigenic potential in vivo. Primary brain tumours showed universal expression of ALDH, with 0.3-28.9% of the cells in various tumours identified as ALDH(+). The proportion of CD133(+) cells within ALDH(+) is higher than ALDH cells. ALDH(+) cells generate neurospheres with high proliferative potential, express neural stem cell markers and differentiate into multiple nervous system lineages. ALDH(+) cells tend to show high expression of induced pluripotent stem cell-related genes. Notably, targeted knockdown of ALDH1 by shRNA interference in BTICs potently disturbed their self-renewing ability. After 3months, ALDH(+) cells gave rise to tumours in 93% of mice whereas ALDH cells did not. The characteristic pathology of mice brain tumours from ALDH(+) cells was similar to that of human brain tumours, and these cells are highly proliferative in vivo. Our data suggest that primary brain tumours contain distinct subpopulations of cells that have high expression levels of ALDH and BTIC characteristics. ALDH might be a potential therapeutic target applicable to primary brain tumours.
authors.affiliation: Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Republic of Korea; Adolescent Cancer Center, Seoul National University Cancer Hospital, Republic of Korea; Department of Neurosurgery, Seoul National University Hospital, College of Medicine, Seoul, Republic of Korea.
authors.forename: Seung Ah
authors.initials: SA
authors.lastname: Choi
authors.affiliation: Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Republic of Korea; Adolescent Cancer Center, Seoul National University Cancer Hospital, Republic of Korea; Department of Neurosurgery, Seoul National University Hospital, College of Medicine, Seoul, Republic of Korea.
authors.forename: Ji Yeoun
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Republic of Korea; Adolescent Cancer Center, Seoul National University Cancer Hospital, Republic of Korea; Department of Neurosurgery, Seoul National University Hospital, College of Medicine, Seoul, Republic of Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Phi
authors.affiliation: Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Republic of Korea; Adolescent Cancer Center, Seoul National University Cancer Hospital, Republic of Korea; Department of Neurosurgery, Seoul National University Hospital, College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyu-Chang
authors.initials: KC
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Seoul National University Hospital, College of Medicine, Seoul, Republic of Korea.
authors.forename: Chul-Kee
authors.initials: CK
authors.lastname: Park
authors.affiliation: Department of Pathology, Seoul National University Hospital, College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung-Hye
authors.initials: SH
authors.lastname: Park
authors.affiliation: Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Republic of Korea; Adolescent Cancer Center, Seoul National University Cancer Hospital, Republic of Korea; Department of Neurosurgery, Seoul National University Hospital, College of Medicine, Seoul, Republic of Korea. Electronic address: nsthomas@snu.ac.kr.
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000368:Aged; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000201:enzymology* / Q000473:pathology*; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase
keywords: Aldehyde dehydrogenase; Brain tumour initiating cell; Primary brain tumours; Stem cell marker